1. Field of the Invention
The present invention relates to a process for preparing ethylcarboxymethylcellulose.
An object of the invention is to provide a novel process for preparing ethylcarboxymethylcellulose on an industrial scale. Another object of the invention is to provide ethylcarboxymethylcelluloses which are novel and possess outstanding properties for use as an enteric coating material.
2. Description of the Prior Art
Ethylcarboxymethylcellulose can be produced by the following three types of processes:
(1) Ethylating carboxymethylcellulose. PA1 (2) Carboxymethylating ethylcellulose. PA1 (3) Reacting two kinds of etherifying agents with cellulose at the same time. PA1 (a) finely dividing the sodium carboxymethyl cellulose to an extent that at least 90 wt. % of the resulting particles pass through a 40-mesh screen, PA1 (b) (i) dispersing the sodium carboxymethyl cellulose in a solvent incapable of mixing with water in a free ratio and subsequently adding to the dispersion a mixture of water and a second solvent miscible with both water and the solvent incapable of mixing with water in a free ratio to adjust the sodium carboxymethylcellulose to water ratio to 75:25 to 50:50 by weight, or (ii) adjusting the water content of the cellulose to a sodium carboxymethylcellulose to water ratio of 75:25 to 50:50 by weight and dispersing the cellulose in a solvent incapable of mixing with water in a free ratio, and PA1 (c) subjecting the resulting dispersion to ethylation.
Among these three basic types of processes, the processes described as type (1) are most useful. However, in all of the previously known processes described as type (1), ethylation of materials having a high degree of carboxymethylation (0.5 or higher in the degree of substitution) not possible. This as will be described below. (Throughout the specification, the term "degree of substitution," to be abbreviated as D.S., means the average number of substituents introduced into the molecule per mole of anhydroglucose unit.)
Japanese Patent Publication No. 53-8751 (1978) discloses a process of the type (1), which nevetheless is none other than the combination of a known process for preparing carboxymethylcellulose and a known process for preparing ethylcellulose, namely, a known process for preparing ethylcellulose in which sodium carboxymethylcellulose is used in place of pulp. Thus the disclosed process is not best suited to the production of ethylcarboxymethylcellulose. Stated more specifically, the process of the publication is characterized by the first step of treating a cellulosic material with an alkali hydroxide and monochloroacetic acid or sodium salt thereof to introduce carboxymethyl groups into the molecule of cellulose and the second step of reacting ethyl chloride with the carboxymethylcellulose under a condition in which the reaction mixture has a water to sodium hydroxide ratio of 20:80 to 50:50 by weight in the initial stage of the reaction. The ethylation of cellulose conducted with ethyl chloride under the initial condition of the water to sodium hydroxide ratio of 20:80 to 50:50 is exactly what is disclosed in thejspecification of British Patent No. 778,732, page 2, etc.
However, carboxymethylcellulose, when allowed to stand in the presence of an alkali and water, generally becomes highly viscous and undergoes blocking. This gives rise to difficulties in permitting penetration of ethyl chloride into the carboxymethylcellulose and effecting the desired degree of substitution of ether, with difficulties also encountered in stirring the reaction system. This tendency becomes pronounced especially when the material is not lower than 0.5 in D.S. of carboxymethyl. In fact, it is impossible to practice the prior patent with materials which are 0.6 or higher in D.S. Further the examples of Japanese Patent Publication No. 53-8751 disclose only the cases in which the D.S. of carboxymethyl is up to 0.49.
Meanwhile, U.S Pat. No. 3,896,108 discloses a process for ethylating carboxymethylcellulose in a slurry containing dioxane, but the carboxymethylcelluloses that are shown in examples are limited to those up to 0.4 in D.S. of carboxymethyl.
From the viewpoint of production of enteric preparations, the solubility of ethylcarboxymethyl cellulose in solvents is critical. The medicinal preparations, such as enzyme preparations, which are unstable in the presence of water must be formulated with use of a solution of a coating material in an anhydrous solvent, whereas the solvents usable for the ethylcarboxymethylcellulose prepared by the conventional processes are limited only to special solvent mixtures because of its solubility. As reported by Motoyama of Froint Sangyo Co., Ltd. in "Yakugyo Jiho" dated Feb. 27, 1978 or as disclosed in Japanese Patent Disclosure No. 52-41213 (1977), ethylcarboxymethylcellulose is insoluble in absolute ethanol but is soluble in a mixture of ethanol and 5 to 20% of water. Although Japanese Patent Publication No. 53-8751 states that ethylcarboxymethylcellulose is soluble in toluene-ethanol (80:20), methylene chloride-methanol (50:50) and ethyl cellosolve-acetone (80:20), nothing whatever is mentioned about its solubility in single anhydrous solvents such as methanol, ethanol, acetone, etc.